Research Article
Volume 13 Issue 10 - 2021
Allopurinol Alters the Expression of Soluble Mediators of Immune Cells in the Brain and Systemic Tissues
Lundrim Marku and Hillar Klandorf*
Department of Animal and Nutritional Sciences, West Virginia University, USA
*Corresponding Author: Hillar Klandorf, Department of Animal and Nutritional Sciences, West Virginia University, USA.
Received: August 30, 2021; Published: September 28, 2021




Abstract

Recent studies have suggested that an increased permeability in the intestine due to a particular insult can induce inflammation in peripheral organs such as the brain. Diminished levels of urate are also linked to oxidative stress in birds and mammals. Urate, a major antioxidant, ameliorates these effects by lowering reactive oxygen/nitrogen species (ROS/RNS). The relationship between reduced urate, the immune system and the pathogenesis of the intestine, the liver or the brain has not been well characterized in avians. Allopurinol, a relatively toxic purine analogue that serves as a xanthine oxidase inhibitor, reduces urate levels which can subsequently induce an inflammation state in the intestine. For this study, White Leghorn Chickens (n = 44) were divided into 11 groups, which constituted of six control groups and five low dose allopurinol treatments fed at 15 mg/kg body weight for 6 weeks. The dose of allopurinol was subsequently increased 5 mg/kg body weight each week for an additional 6 weeks. Blood samples were obtained from the brachial vein in the wing and liver panel blood chemistries performed to characterize the inflammations state. At the end of the study, tissues were removed after cervical dislocation and placed in liquid nitrogen. Expression levels of TNF-α, IL-6, FASLG and COX-2 were subsequently investigated in the intestines, liver and midbrain. Results showed that urate was reduced in all treatment groups regardless of time (p < 0.05), treatment groups exhibited reduced amounts of bile acids (p < 0.05) while female treatment groups exhibited increased amounts of LDH and AST from week 2 to the end of the study (p < 0.05). The effect of allopurinol on the intestines of females showed that expression of IL-6, COX-2, TNF-α expression was increased (p < 0.05). TNF-α expression in the liver decreased in both females and males by 3 and 2-fold respectively (p < 0.05). FASLG expression in the liver decreased 2-fold in both male and females respectively (p < 0.05). The effect of allopurinol on the midbrain of females revealed that IL-6 expression decreased (p < 0.05) whereas in males IL-6 expression increased by almost 2-fold (p < 0.05). Notably, COX-2 expression in the midbrain increased in females and males by 7 and 10-fold (p < 0.05). In conclusion, the elevated body temperatures of birds may accentuate the pathogenesis of complications induced by allopurinol and so may be a model for future studies investigating neurodegenerative disease progression.

Keywords: Allopurinol; Chickens; Il-6; TNF-Alpha; Brain Inflammation; Gut Inflammation

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Citation: Lundrim Marku and Hillar Klandorf. “Allopurinol Alters the Expression of Soluble Mediators of Immune Cells in the Brain and Systemic Tissues”. EC Neurology 13.10 (2021): 78-90.

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